Unintentional drug overdose death rates in the U.S. have more than tripled since 1990.

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4 Rate per 100,000 Population Unintentional drug overdose death rates in the U.S. have more than tripled since *Deaths are those for which poisoning by drugs (illicit, prescription, and over-the-counter) was the underlying cause. Source: Centers for Disease Control and Prevention,

5 Rate per 100,000 Population Unintentional Poisoning Death Rates, Oklahoma and the United States, Oklahoma US Source: WISQARS, Centers for Disease Control and Prevention 5

6 Rate per 100,000 Population Unintentional Poisoning and Motor Vehicle Crash Death Rates, Oklahoma, Unintentional Poisoning MVC Source: WISQARS, Centers for Disease Control and Prevention 6

7 Rate per 100,000 Population Mortality Rates by Age Group and Gender, Unintentional Poisoning, Oklahoma, < Age Group Males Females Source: OSDH, Injury Prevention Service, Unintentional Poisonings Database (Abstracted from Medical Examiner reports) 7

8 Number of Deaths Deaths Involving Prescription Drugs, Illicit Drugs, or Alcohol by Year of Death, Unintentional Poisoning, Oklahoma, All poisonings Prescription Alcohol Methamphetamine Cocaine Year of Death Source: OSDH, Injury Prevention Service, Unintentional Poisonings Database (Abstracted from Medical Examiner reports) 8

9 Source: OSDH, Injury Prevention Service, Unintentional Poisonings Database (Abstracted from Medical Examiner reports) 9

10 Medications Most common medications (number of deaths): Hydrocodone (632) Oxycodone (627) Alprazolam (620) Methadone (545) Morphine (393) Medication Type Number Rate Prescription medication Narcotic analgesic Anti-anxiety Muscle relaxant Antidepressant Tri-cyclic antidepressant Non-narcotic analgesic Antipsychotic Respiratory Hypnotic/sedative Antiemetic CNS stimulant Other** Over the counter

11 Figure 7. Unintentional Poisoning Death Rates by County of Residence 1, Oklahoma, Cimarron Texas Beaver Harper Woods Alfalfa Grant Kay Osage Washington Nowata Craig Ottawa Woodward Major Garfield Noble Pawnee Rogers Mayes Delaware Rates per 100,000 population Elis Dewey Blaine Kingfisher Logan Payne Creek Tulsa Wagoner Cherokee Adair Top Five Counties No Deaths State rate 2 : 17.0 U.S. rate 3 : 10.6 Harmon 1 County of residence was unknown for 21 persons Medical Examiner data NCHS Vital Statistics System, retrieved from CDC WISQARS Roger Mils Beckham Greer Jackson Custer Washita Kiowa Tilman Caddo Comanche Cotton Canadian Grady Stephens Jefferson Oklahoma McClain Cleveland Garvin Carter Love Potta - watomie Murray Lincoln Marshal Seminole Pontotoc Johnston Okfuskee Hughes Coal Bryan Okmulgee Atoka Pittsburg McIntosh Muskogee Pushmataha Choctaw Latimer Haskel Sequoyah Le Flore McCurtain 11

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13 Pain Intensity Rating Scales Visual Analogue Scale (VAS) No pain Worst pain Numerical Rating Scale No pain Categorical Scale None (0) Mild (1 4) Moderate (5 6) Severe (7 10) 10 Worst pain imaginable (Cleeland, 1991; Jacox et al, 1994) 13

14 Pain Intensity Rating Scales Pain Faces Scale 0 No hurt 2 Hurts just a little bit 4 Hurts a little bit more Brief Pain Inventory 6 Hurts even more 8 Hurts a whole lot 10 Hurts as much as you can imagine Shade areas of worst pain Put an X on area that hurts most (Cleeland, 1991; Wong et al, 2001) 14

15 GOAL OF THERAPY Pain is recognized as the 5 th vital sign 15

16 W.H.O. 3 STEP ANALGESIC LADDER By the Clock 1 Non-opioid +/- adjuvant 2 Weak opioid +/- adjuvant 3 Strong opioid +/- adjuvant (Remember combo opioids have APAP limitations!) 16

17 Plasma Concentration Routes of Administration IV SC / IM Cmax po / pr 0 Half-life (t 1/2 ) Time 17

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19 Equianalgesic Table ORAL (mg) Drug Parenteral (mg) 30 Morphine Hydromorphone Oxycodone Codeine Demerol 75 Numerous equianalgesic tables published. The best recommendation is to pick one and use it. 19

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21 Fentanyl Patch Guidelines 21

22 Fentanyl Patch Guidelines 22

23 The Pain Management Cases 23

24 Clinical Questions #1 Breakthrough pain dosing should be individualized, but a guide for determining the initial dose of bolus I.V. medication for a patient receiving a long acting oral form of morphine is that the initial breakthrough dose is what percentage of the total daily long-acting morphine dose? a. 10% b. 20% c. 50% d. 100% 24

25 Answer #1 a. 10% Rationale: 10% would be the minimum dose, Titrated to effect. The range is 10-20% 25

26 Breakthrough Pain Patients on long-acting med always need second, short-acting med, for breakthrough pain to take Q 4 hours or less. Generally, dose of breakthrough opioid should be: 10% of 24 hour dose of analgesics and made available Q 2-4 hours. Example: MS Contin 60mg q12hrs breakthrough dose should be immediate release morphine (MSIR), mg Q 2-4 hrs prn. Total morphine dose in 24 hours = 120mg; 10% is ~12mg 26

27 Clinical Question #2 What is the maximum number of tablets of hydrocodone/acetaminophen 5 mg/500 mg (e.g., Vicodin ) you can safely prescribe for a 24 hour period. a. 4 b. 6 c. 8 d. There is no ceiling dose/maximum 27

28 Answer #2 c. 8 Rationale: 4,000mg of acetaminophen in 24 hours is safe for most patients, BUT ceiling dose may need to be modified significantly or the drug not used in patients with: renal or liver disease history of significant alcohol intake consider starting at 50% of standard ceiling dose for elders. 28

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30 Clinical Question #3 Ms. Jones, a 40 yr. old women with stage IV ovarian cancer reports mild to moderate burning pain in her hands and feet. Ibuprofen has not been effective. You suggest: a. A COX-2 inhibitor b. Topical capsaicin c. A steroid d. An adjuvant with activity in neuropathic pain 30

31 Answer #3 d. An Adjuvant with activity in neuropathic pain Pain characterized by sharp, shooting, electric shocks, parethesias, dysesthesias, cold extremities Neuropathic pain often responds poorly to NSAIDs and opioids 31

32 Drugs for Neuropathic Pain opioids antidepressants anticonvulsants local anesthetics steroids other 32

33 Antidepressants Tricyclic antidepressants Analgesic effects separate from anti-depressant effects. Amitriptyline: most studied, but most side effects Nortriptyline & desipramine: better tolerated, less well studied SSRIs: little evidence of analgesic effect. SNRI s inhibit both norepinephrine and serotonin reuptake efficacy in neuropathic pain syndromes or pain associated with depression (duloxetine [Cymbalta ], venlafaxine [Effexor ]) 33

34 Anticonvulsants Agents for neuropathic pain gabapentin (Neurontin ) pregabalin (Lyrica ) CONTROL (C-V) clonazepam (Klonopin )---CONTROL (C-IV) Other newer agents Start low, go slow Watch for side effects Monitor serum levels, if available 34

35 Adjuvants to Opioid Therapy Adjuvant Alpha agonists Anticonvulsants Antihistamines Benzodiazepines Bisphosphonates Corticosteroids NSAIDs / COX-2 I Tricyclic anti-depressants Common indication Neuropathic pain Neuropathic pain Nausea, pruritus Pain w/anxiety Bone pain (cancer) Bone pain (cancer) Musculoskeletal pain Neuropathic pain 35

36 Clinical Question #4 Mr. Simpson, a 63 yr. old man with advanced prostate cancer has been stable on oral morphine 30 mg every 4 hours. He is now NPO and you are going to switch him to IV morphine. The correct IV dose is: a. 4 mg IV q 4 hours b. 6 mg IV q 4 hours c. 10 mg IV q 4 hours d. 30 mg IV q 4 hours 36

37 Answer #4 c. 10 mg IV q 4 hours Rationale: Equianalgesic ratio for morphine is 1 mg IV = 3 mg PO. When writing start time for the first dose, consider time of last oral dose. ORAL DOSE (MG) MED PAREN- TERAL DOSE (MG) 30 Morphine Hydromorphone (Dilaudid ) Oxycodone Hydrocodone -- 37

38 Parenteral Opioids IV is the route of choice if access is available. There is NO indication for IM opioids (painful, no benefit over SQ route) All standard opioids can be given SQ, by either bolus dose or by continuous infusion. PCA (basal rate plus a patient initiated dose) is an effective and well accepted modality; either IV or SQ. 38

39 Parenteral Opioids (cont.) IV or SQ bolus doses have a shorter duration of action than oral doses; typically 1-3 hours. The peak effect from an IV bolus dose is 5-15 minutes. Dose escalation of parenteral opioids is the same as with oral always by a percentage of the starting dose. 39

40 Plasma Concentration Routes of Administration IV SC / IM Cmax po / pr 0 Half-life (t 1/2 ) Time 40

41 Clinical Question #5 Mrs. Smith has advanced cervical cancer. She has been taking Percocet-5 (2 tablets PRN) for pain with good effect. The patient is now NPO & is requiring something for pain. An appropriate starting dose of PRN IV morphine is approximately: a. 2 mg b. 3 mg c. 4 mg d. 5 mg e. 6 mg 41

42 Answer #5 c. 4 mg IV morphine Rationale: Most equianalgesic tables use a ratio of 20 mg po oxycodone = 10 mg IV morphine. Mathematically, answer is 5 mg IV morphine. Clinically, account for possible incomplete cross-tolerance, so reduce the dose by about 25%-50%. 4 mg is a convenient dose of IV morphine. We might also have rounded down to 3 mg. 4 mg is almost certainly safe and analgesically appropriate for opioid non-naïve patient. 42

43 Clinical Question #6 Mr. Johnson, a 69 yr. old patient with metastatic prostate cancer to the lumbar spine is taking OxyContin (sustained release oxycodone) 100 mg every 8 hours. What should be the opioid for his breakthrough pain and at what dose and interval? a. Oxycodone 30 mg PO every 4 hours b. Oxycodone 30 mg PO every 8 hours c. Morphine 10 mg PO every 4 hours d. Morphine 10 mg IV every 8 hours 43

44 Answer #6 a. Oxycodone 30 mg PO every 4 hours Rationale: In general, keep PRN, short acting opioid the same drug as the long-acting opioid. Starting dose for breakthrough pain is 10% of the total daily dose (and you can always titrate). Here total daily dose = 300 mg, so 10% of this = 30 mg. The PRN interval should never be longer than the expected analgesic duration (~4 hours in this case), and can often be less. 44

45 Short Acting Opioids Oral dosing: onset in min peak effect in minutes duration of effect 2-4 hours Can be dose escalated or re-administered every 2-4 hours for poorly controlled pain General guideline: Moderate pain: increase 25-50% Severe pain: increase by % 45

46 B. Short Acting Opioids Parenteral or Oral: morphine hydromorphone (Dilaudid ) Codeine Onset & duration of action depends on route administration Oral only: oxycodone (Percocet, Tylox ) hydrocodone (Vicodin Lortab, Lorcet, Norco) propoxyphene (Darvon, Wygesic ) Note: hydrocodone is only available as a combination product. 46

47 Clinical Question #7 Ms. Spears is reporting 7/10 pain now in her left leg. She had vomited after her last pain medication, morphine 10 mg IV. What is your next analgesic order? a. Dilaudid (hydromorphone) 1.5 mg IV b. Fentanyl Patch 25 mcg/hr q72 hours c. Dilaudid 8 mg PO d. Percocet 5/325 three tablets 47

48 Answer #7 a. Dilaudid (hydromorphone) 1.5 mg IV Rationale: With severe pain we need rapid onset option. Onset too slow with Fentanyl patch and orals. IV morphine plus an antiemetic might be considered, but easier option - change to another opioid (different patients have different side effect responses to various opioids). Hydromorphone 1.5 mg IV is approx. equianalgesic to 10 mg IV morphine. As patient currently in severe pain, reducing dose for potential incomplete cross tolerance not necessary. 48

49 Opioid Dose Escalation Always increase by a percentage of the present dose based upon patient s pain rating and current assessment % increase 25% increase 25-50% increase Severe pain 7-10/10 Moderate pain 4-6/10 Mild pain 1-3/10 49

50 Frequency of dose escalation The frequency of dose escalation (oral opioids) depends on the particular opioid Short acting oral: q 2-4 hours Long acting oral, except methadone: q 24 hours methadone: q 72 hours transdermal fentanyl: q 72 hours. 50

51 Clinical Question #8 Mr. McDonald comes to your floor in excruciating pain (10/10). He receives morphine 4 mg IV, but reports no relief at all after 15 minutes. The intern or fellow then orders morphine 6 mg IV. After another 20 minutes the patient reports that she still has no relief. You note that the patient is wide awake (no sedation) with continued 10/10 pain. What would you recommend? a. Tell the patient that the interval between doses is 4 hours and they will have to wait b. Administer another dose of morphine 6 mg IV in one hour c. Administer another dose of morphine 9-12 mg now d. Call for a pain or palliative care consult 51

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53 Clinical Question #8 Mr. McDonald comes to your floor in excruciating pain (10/10). He receives morphine 4 mg IV, but reports no relief at all after 15 minutes. The intern or fellow then orders morphine 6 mg IV. After another 20 minutes the patient reports that she still has no relief. You note that the patient is wide awake (no sedation) with continued 10/10 pain. What would you recommend? a. Tell the patient that the interval between doses is 4 hours and they will have to wait b. Administer another dose of morphine 6 mg IV in one hour c. Administer another dose of morphine 9-12 mg now d. Call for a pain or palliative care consult 53

54 Answer #8 c. Administer another dose of morphine 9-12 mg now. Rationale: Patient has no unacceptable side effects, so no immediate reason to change to another drug. Patient is in a pain crisis. We should titrate aggressively (i.e., % increase in each dose at approximately 15 minute intervals) until a response is observed. Note:some protocols for pain crisis in cancer patients suggest that 1-2 doses of ketorolac (Toradol ) 30 mg IV be considered (if not otherwise contraindicated) in addition to the opioid. 54

55 Clinical Question #9 Ms. Torres, a 45 yr. old woman with colon cancer metastatic to the liver, had been admitted for uncontrolled pain. Her pain is now controlled and stable on PCA morphine of 10 mg/hr. The boluses are 5 mg q15 minutes PRN and work very well but she rarely needs to use the bolus doses for breakthrough pain. She is to be discharged home on oral opioids. What opioid/formulation and what dose would you recommend? a. MS Contin 120 mg PO Q 12 hours b. MS Contin 240 mg PO Q 12 hours c. MS Contin 360 mg PO Q 12 hours d. Fentanyl patch 50 mcg Q 72 hours e. Dilaudid 8 mg PO Q 8 hours 55

56 Equianalgesic Doses: Opioid Analgesics ORAL DOSE (MG) ANALGESIC PARENTERAL DOSE (MG) 30 Morphine Hydromorphone (Dilaudid ) Oxycodone Hydrocodone -- 56

57 Answer #9 c. MS Contin 360 mg PO every 12 hours Rationale: Patient already on morphine, so use same opioid. Using long-acting formulation is the oral equivalent of a continuous infusion. Total daily dose of morphine IV is 240 mg and the oral equivalent is 720 mg of morphine, can be given as 360 mg of MS Contin PO every 12 hours. 57

58 C. Long Acting Opioids Oral morphine: MS Contin Kadian Oramorph SR oxycodone Oxycontin Oxycodone SR oxymorphone Opana SR methadone Transdermal Fentanyl Patch (Duragesic ) Dosing Q 72 hours 58

59 Clinical Question #10 What breakthrough pain opioid/formulation would you recommend for Ms. Torres if she takes MS Contin 360 Mg Q 12 hours? a. Morphine elixir 20 mg PO every 2-4 hours PRN b. Morphine immediate release tablets 40 mg PO q 2-4 hours PRN c. Morphine immediate release tablets 60 mg PO q 2-4 hours PRN d. Morphine immediate release tablets 70 mg PO q 2-4 hours PRN 59

60 Answer #10 d. Morphine immediate release tablets 70 mg PO every 2-4 hours PRN. Rationale: Breakthrough pain requires a short-acting formulation. Preferable to use same opioid as long-acting. PRN initially 10% of the total daily dose = 10% of 720mg = 72mg. Dosing interval is q2-3h PRN. We don t expect that pts will need to take 12 doses in 24hr (our pain regimen would be really off). If patient requires >5 PRN doses/day, either the PRN dose needs adjusting or the basal dose or both. 60

61 National Updates 61

62 National Updates turnthetiderx.org 62

63 Oklahoma Updates 63

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66 Office-Based Prescribing 66

67 QUESTIONS? 67